Trip aborting cyproheptadine (periactin)

[_Trip_]

Hi all after a bit of digging around the forum, to my surprise I noticed there is little information on cyproheptadine (AKA periactin). A simple over the counter first generation antihistamine. It is usually used as a first line treatment in serotonin syndrome in emergency settings.

However, it has good potential use for damping bad trips. LSD/psilocin/DMT/ Mescaline act as agonist and have high binding affinities to 5-HT1A, 5-HT2A, 5-HT2C receptors (just to name a few). These are thought to be some of the main receptors involved in their effects.

Cyproheptadine has a high affinity for 5-HT receptors however it acts as an antagonist and blocks these receptors, so agonist like LSD etc can't bind to it. At 4mg (3 times a day) cyproheptadine blocks 85% of 5-HT2 receptors, at 6mg 95% are blocked. Obviously there are other receptors that come into play. Cyproheptadine also has binding affinities for some dopamine receptors and other serotonin sites (and obviously histamine sites) however so do some of the aforementioned pyschedlics. Regardless this drug stands out as a safer alternative and often more easily available medication for 'aborting' trips compared to benzos.

12mg is usually a standard dose for suspected serotonin syndrome.

It takes 1-3 hours to peak in the blood stream, 8hr half life and has a LD50 in rats of 295mg/kg making it a very safe drug. Bare in mind as a first generation antihistamine it also has sedative effects.

It however could interact with MAOI's particularly pharmaceutical MAOI's as it also has anticholinergic effects so adverse effects like: blurred vision, constipation, dry mouth, urine retention, tachycardia, nasal congestion or dry throat could ensue.

All in all there is good potential use for helping dampen bad trips worthy of further discussion.

 

[Toshido]

Well done on the research! Nice to know that there is something safer than benzos. It's hard to find information on how much Alprazolam you would need per 100 microrgrams of LSD or milligrams of mescaline or grams of mushrooms, so something safer like this could be manageable.

 

[DoingKermit]

Thanks for doing some research into this, Trip. Do you have any papers or journals with further information?

This is all I could find in relation to LSD and cyproheptadine.

Thanks

 

[_Trip_]

There's almost nothing in the literature on cyproheptadine and psychedelics.

I attached the full study below. It's quite interesting.


There's some good articles on it's effectiveness for serotonin syndrome and its pathophysiology. However, there are also other reviews suggesting it needs more evidence. Regardless there are a number case studies and reviews stating its effectiveness and it is still used as a first line treatment.
For a drug that has antagonist effects on particular serotonin receptors it would theoretically have a decent effect on blocking LSD/ psilocin/ etc on some sites.

I've only ever heard anecdotal reports of people using it and stating it indeed has a dampening effect. I can't confirm this myself and as stated there is no studies on it.

There will likely never be one compound to completely abort all aspects of a trip, but there are medications that can/ may ease certain aspects. I think its worth discussing the safest and most available medications from a safety POV.

 

[Toshido]

I had a friend who had a terrible experience on 5g of mushrooms while we were at a music festival. There were 3 reasons for this.

1) Without consulting us, he ate what was in a bag he had on his person without measuring it, thinking it was "1 helping" of mushrooms.

2) It was his first time on any psychedelic aside from cannabis.

3) A defective firework went off in close proximity.

TL;DR: He ended up at the hospital and they pumped him full of benzos, he doesn't remember anything and never tripped again.

-------------------------

Full story,

We were sitting in lawn chairs in a circle, about 8 of us, and we had each consumed anywhere between 1.75g and 3.5g of mushrooms. Except for our friend who I will call Drew. He proclaimed that he ate the contents of a bag that had 5g written on it. We wanted to panic and explain to him what he had just done, but we decided to keep our cool and let it ride out as to not to scare him.

About 20-30 minutes in he kept standing up and then sitting back down muttering to himself "it's all good." We were at All Good music festival. He was worried about where another one of our friends was and we assured him they were fine and that he should enjoy himself. Then he got up out his chair one last time and raised his hands up in the air and it exclaimed "IT'S ALL GOOD!" in a surrendering, confident kind of way.

Problem was a gigantic firework exploded not 10 ft away from us that only made it maybe 15ft into the air before exploding RIGHT as our friend screamed "IT'S ALL GOOD!" and it made him snap.

He ran off at full speed. Myself and another buddy caught up to him but we couldn't contain him, he was the biggest of all of us and he was strong. All we heard him say before we lost sight of him was that he "needed to save everyone from the impending meteor shower".

We never saw him again after that, but I spoke with him on the phone the next day while he was at the hospital with no memory of what had happened. However, another friend of mine who was a volunteer security guard/staff member who ALSO knew Drew told me what had unfolded.

Drew jumped into someones convertible with 2 people in it who were just arriving to the festival just then and proceeded to attack the people like a zombie. Security was called and it took 4 people to restrain him while they waited for an on site ambulance to take him to the hospital.

I'm guessing that in the ambulance they gave him a bunch of benzos because he doesn't remember anything. Fortunately, he doesn't have any permanent psychological damage and is the same as always.

That's why I'm all about trip killers, because had they not "killed his trip" he could very well have permanent damage to his psyche.

All in all, it was his errant decision to consume a drug without having proper knowledge of dosage that led him to that awful experience.

 

[DoingKermit]

There's almost nothing in the literature on cyproheptadine and psychedelics.

I attached the full study below. It's quite interesting.


There's some good articles on it's effectiveness for serotonin syndrome and its pathophysiology. However, there are also other reviews suggesting it needs more evidence. Regardless there are a number case studies and reviews stating its effectiveness and it is still used as a first line treatment.
For a drug that has antagonist effects on particular serotonin receptors it would theoretically have a decent effect on blocking LSD/ psilocin/ etc on some sites.

I've only ever heard anecdotal reports of people using it and stating it indeed has a dampening effect. I can't confirm this myself and as stated there is no studies on it.

There will likely never be one compound to completely abort all aspects of a trip, but there are medications that can/ may ease certain aspects. I think its worth discussing the safest and most available medications from a safety POV.

Thanks for the reply. The fact that is readily available OTC is quite an appealing aspect. I have also read reports of people taking antihistamines and not experiencing any softening of the effects. As we know, there are lots of factors to consider, so a proper study would indeed be helpful.

 

[_Trip_]

I agree, remember other antihistamines target very different receptors (with exception of H1/H2). So in cases where pyschedlics and antihistamines are used together they will likely not have a softening effect as you have read, it's very dependant on the drug molecule and the corresponding receptors it affects. Keeping in mind second generation antihistamines don't cross the blood brain barrier and therefore would be useless in damping trips (this is why first generation antihistamines have sedative effects they do cross the blood brain barrier). But in theory periactin (a first gen) shows promise and I think it's worth asking if anyone has used this combination purposely or by accident.

Different antihistamines have some noteworth effects than just allergy control, clemastine has shown promise in remylination on neuron connections for people suffering neurological diseses like MS.

 

[DoingKermit]

I agree, remember other antihistamines target very different receptors (with exception of H1/H2). So in cases where pyschedlics and antihistamines are used together they will likely not have a softening effect as you have read, it's very dependant on the drug molecule and the corresponding receptors it affects. Keeping in mind second generation antihistamines don't cross the blood brain barrier and therefore would be useless in damping trips (this is why first generation antihistamines have sedative effects they do cross the blood brain barrier). But in theory periactin (a first gen) shows promise and I think it's worth asking if anyone has used this combination purposely or by accident.

Different antihistamines have some noteworth effects than just allergy control, clemastine has shown promise in remylination on neuron connections for people suffering neurological diseses like MS.

Ah yes, good point and great knowledge, Trip. I appreciate the feedback. I'm going to ask my psychiatrist friend, who works in psychedelics, what he thinks about all this.

 

[_Trip_]

Would be great to get his opinion!

 

[_Trip_]

To build on this thread and I'm sure it's been discussed before but ketanserin a blood pressure medication can completely stop a LSD trip according to one study. Interesting if it has any effect on other psychedelics.

 

[Varallo]

I have never taken a drug to stop a trip but would love to have something like that. I live a very busy life and the amount of times that I would have liked to take a hit of lsd but couldn’t get a 12 hour block of time to trip are countless. A relatively safe antihistamine would be a great option, and for some people who have a very difficult time other more serious drugs would be an option.

So I have been following this subject with great interest for some time now and think it would make a great collaborative research project to test some of these drugs and see how and in what way they work.

Just some Questions that could be answered would be:

- What drugs are working for what psychedelic, taking contraindications with harmalas into consideration.
- How long does it take to get diminished effects.
- How drastic is the reduction
- Dosage

We could think about a test protocol, so for example you would take a 100, 200, 400 microgram of lsd and then take the tripstop drug at 2 or 4 hours in. Then record the effects.

We could play with different dosages of both and see what happens.

Just some thoughts on the subject, if we could get a small group together and test some of the hypothesis I would be willing to test some of them out in the name of science.

Drugs to test would be first generation antihistamines and the commonly mentioned seroquel or trazodone.

 

[_Trip_]

Agreed, i hope to see this thread or even if we start another, filled with reports on trip "stoppers". Ketanserin sounds like a very promising drug where as periactin sounds more like a dampener but I've only read reports of people taking it prior to tripping. Nevertheless, periactin is more readily available. I might try periactin next time I do smokeable pharmahusca.

I have access to seroquel, olazapine, and a couple benzos. But as mentioned harmala needs to be taken into consideration for some of these.

 

[Varallo]

It appears that some people are doing research on Ketanserin testing the shortening of the effects with ketanserin, ClinicalTrials.gov other than that it seems like this is not really an easy obtainable drug and most of the research I see is on intravenous administration, which would make it not only difficult to get but also impossible to administer safely if tripping by yourself.

I have tried combining lsd with up to 20 mg of Valium, without any tolerance, and did not have the idea that it did much to stop the trip, it does however make for a smooth landing.

 

[_Trip_]

Yes i was just researching the same thing it does not look obtainable at all.

 

[Transform]

To build on this thread and I'm sure it's been discussed before but ketanserin a blood pressure medication can completely stop a LSD trip according to one study. Interesting if it has any effect on other psychedelics.

Ketanserin is used as a standard 5-HT antagonist in receptor studies with serotonergics. Crops up a lot in 'our kind of literature'.

 

[DarkSonic]

Hi there.

Just wanted to post a real world experience with Cyproheptadine (Zyactin brand name). It is a 100% trip killer for me. Went from tripping deep on 150mcg LSD to totally sober in 30 minutes.

Its a unique anti histamine with very strong antagonist affinity for 5ht receptors. The same receptors most classic psychadelics bind to. If you look up its binding affinity profile, it has 2x stronger affinity than LSD on 3 different 5HT-x receptors. Other anti histamines dont do this or dont come anywhere close to the binding strength.

Have tried Xanax many times before and it simply calms me and dulls the intensity, but the trip continues. This is a total pharmaceutical abort button.

Doesnt have to just be used for bad trips, but also if you simply need to sober up or if youve had enough from longer acting psychadelics like mescaline or lsd.

Use it sublingually (dissolve under tongue and hold it there) for fastest effect. I feel the effects in 15m as the trip starts to drastically fade and completely clear headed and sober in 30m

1x 4mg tablet completely aborted an LSD trip for me, but dosage on packet is indicated upto 12mg if needed (3 tabs).

Its available OTC in Oz, Canada, some countries in Europe too. Script required in USA. It is freely available in my country.

I don't trip without it now and its a lifesaver as I suffer from anxiety for more than the average person.

Its a typical first gen anti histamine so you will be drowsy and sleep like a log after(just like Benadryl)

Just knowing I have it in my pocket now and I can abort whenever I want makes for a far more calmer and reassuring trip. Ironically once you have that assurance you will find more challenging trips far more manageable and wont need to abort them to begin with.

I posted this on Reddit and it gained huge traction as many people found this info very pertinent and useful. It then got locked and deleted as 'medical advice', which it wasnt. But I understand they simply covering themselves from any legal issues.

Im not giving any medical advice or opinion, simply my own subjective experience. Always consult your own doctor, priest and spirit guide before taking any medications.

Hope this helps someone.

 

[_Trip_]

Thanks for reporting DarkSonic, very interesting. I did theorise it would likely be a good trip aborter and was surprised how little information was on it in regards to psychedelics when i first looked into it. Olanzapine would be another good one. But periactin would be a 'safer' firstline medication if its this effective.

It's such a safe medication and as a first gen antihistamine it crosses the BBB and also aids in sleep, to help sleep off a bad trip.
Although like all first generation antihistamines taking too much in a short period is linked to dementia later in life, regardless a once off would be very safe especially in comparison to the harm a bad trip can psychologically cause.

 

[DarkSonic]

Although like all first generation antihistamines taking too much in a short period is linked to dementia later in life, regardless a once off would be very safe especially in comparison to the harm a bad trip can psychologically cause.

That does not appear to be accurate. This is likely what you are referencing below.

"A 2015 study published in JAMA Internal Medicine found that cumulative use of anticholinergic drugs, including some first-generation antihistamines, over years (especially at high doses) was associated with a higher risk of dementia in older adults. The study tracked people over 65 and calculated their exposure based on "anticholinergic burden." Higher exposure correlated with a modestly increased risk of Alzheimer’s or other dementias. However, the study didn’t prove causation—only an association—and it included other anticholinergic drugs, not just antihistamines."

So this does not appear to be relevant to only Cyproheptadine and sporadic use such as in our case. First gen anti histamine are generally well regarded as a safe class of drugs, albeit known for side effects like drowsiness and sleep.

 

[blig-blug]

Cyproheptadine is related structurally to ketotifen, and ketotifen also seems to have affinity for the 5-HT2 receptors, although I couldn't find information specific to the 5-HT2A. It could be interesting to test ketotifen as well, as in those countries where cyproheptadine is not available OTC, it will likely be much easier to obtain ketotifen, due to its use by some bodybuilders in order to counteract clenbuterol tolerance.

 

[_Trip_]

That does not appear to be accurate. This is likely what you are referencing below.

"A 2015 study published in JAMA Internal Medicine found that cumulative use of anticholinergic drugs, including some first-generation antihistamines, over years (especially at high doses) was associated with a higher risk of dementia in older adults. The study tracked people over 65 and calculated their exposure based on "anticholinergic burden." Higher exposure correlated with a modestly increased risk of Alzheimer’s or other dementias. However, the study didn’t prove causation—only an association—and it included other anticholinergic drugs, not just antihistamines."

So this does not appear to be relevant to only Cyproheptadine and sporadic use such as in our case. First gen anti histamine are generally well regarded as a safe class of drugs, albeit known for side effects like drowsiness and sleep.

To be clear when I said a short period I did not mean weeks or months, I meant over a decade or so. Which is a short period over a lifetime. I feel this pertains to dementia as it is a disease that happens later in life, over a long lifetime. So it is obviously accumulative. It is a disease that has many contributing factors. First generation antihistamines are being studied as one of those factors. There are quite a few other studies on this now other than the one you quoted.

Indeed I was likely thinking of that study as it states they followed participants medication use over a 10 year period (Which is maybe why I had a decade in my mind). Interesting to note, iirc, such drugs are know to increase dementia symptoms in people with dementia.

I never said it wasn't safe nor that it is relevant to only cyproheptadine as you stated? I clearly said first generation antihistamines i did not single it out. I also didn't say it causes, I said is linked to. If im being honest your post reads like a chat gpt reply.

I also do not see a study passing ethics balances and checks if they were to say give first generation antihistamines to a group of 20 year olds everyday for 10 years to see if it induces early onset dementia. That is to say it would be hard scientifically gauge the damage long term use could do over a long period in a large sample group of young healthy people, especially as many users of all ages use such medications as regular sleep aids.

I would therefore respectfully argue what I wrote is accurate. In addition, I think it is good that people have access to information on potential risks no mater how big or small to mitigate risk and make their own informed decisions regardless of the drug. I hope by pointing this link out people can be mindful.

PS. I have editing my post to read "extended period" to better reflect what I meant. Thank you for pointing this out.